DESCRIPTION (Adapted from the applicants abstract): The overall goal of this project is to understand the molecular pathogenesis of group A streptococcus. High priority will be given to testing the impact of the C5a peptidase (SCPA) on the capacity of streptococci to cause infection in three animal models. A second, very important objective is to confirm that SCPA protein can induce immunity to infection. A new direction of this project is to investigate the impact of surface proteins on the trafficking of streptococci to lymphoid tissues in infected animals. Investigations from our laboratory indicate that streptococcal infections are a complex, multi-stage process. Regulated expression of multiple factors contributes to a pathogen's capacity to avoid the innate and adaptive immune defenses of their host. Understanding the importance of C5a peptidases in microbial virulence will expand the investigators knowledge of host-parasite relationships. The recent resurgence of serious complications and the fact that 10% of all office calls in a general medical practice in the United States are associated with group A streptococcal infections, highlight the need for an effective vaccine to prevent these infections. A broadly effective, safe vaccine could result from this study of group A streptococcal C5a peptidase.